JPS6187678A - Manufacture of 3,4-dihydro-2,2-dioxo-3-methyl-1, 2-benzoxatiin-8-yl sulfonamide - Google Patents

Abstract

A novel process for the preparation of 3,4-dihydro-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide of the formula I <IMAGE> (I) reacting a 5-halo-2,3-dihydro-2-methylbenzo[b]furan of the formula II <IMAGE> (II) wherein Hal is chlorine or bromine, with chlorosulfonic acid to give a 6-halo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonyl chloride of formula III <IMAGE> (III) wherein Hal is chlorine or bromine, converting this sulfonyl chloride with ammonia into a 6-halo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide of formula IV <IMAGE> (IV) wherein Hal is chlorine or bromine, dehalogenating this sulfonamide with hydrogen in the presence of a tertiary amine and a noble metal catalyst, and hydrogenating the resultant 2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide of formula V <IMAGE> (V) with hydrogen in the presence of a noble metal catalyst.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention provides a novel method for producing 3,4-dihydro-2,2-dioquine-3-methyl-1,2-pe/zoxathiin-8-ylsulfonamide. Regarding.

(Conventional f3 technique) 5,4-dihydro 2.2 obtained by the method of the present invention
-Dioquino-5-methyl-1,2-benzoxathiine-
8-yl sulfonamides are valuable intermediates for the production of sulfonylurea herbicides and plant bio-ve regulators. The compounds and their biological properties are known, for example from European Patent Publication EP-A, 99 559.

Methods for producing compounds having a 1.2-be/zoxathiine structure are described in various publications, such as J. SulfurChem.
, , A, Volume 2, Bian 4. Pages 249-255 (1
972) or EP-A-107979.

(Problems to be Solved by the Invention) However, the methods used in these methods involve a relatively large number of reaction steps, and are therefore not well suited for the production of Taikimata.

Therefore, there is a need for a simple synthetic method that consists of one or several reaction steps and can yield the desired intermediate in high yield.

(Means for solving the problem) Surprisingly, in the present invention, the following formula ■: (wherein H
5-halo 2,3-dihydro-2-methylbenzo [b) represented by al represents a chlorine atom or a bromine atom)
Furan is reacted with chlorosulfonic acid to produce 6-halo2,2-dioquino-5-methyl-1,2-benzoxathiin represented by the following formula (1): (wherein Ha/ii represents a chlorine atom or an ilt bromine atom) -8-ylsulfonyl chloride is produced, and this sulfonyl chloride is converted into 6-halo 2,2-dioxo-3-methyl-1,2-benzoxathiin represented by the following formula (Hal Fi represents a chlorine atom or a bromine atom) using ammonia. -8-ylsulfonamide, which is de-logenated with hydrogen in the presence of a tertiary amine and a noble metal catalyst;
The following formula I is obtained by adding 65 hydrogen atoms to the obtained 2,2-dioxo-6-methyl-1,2-penzoxatii/-8-ylsulfonamide represented by the following formula (1) in the presence of a noble metal catalyst: 3,4-dihydro-212-dioxo-5 represented by
-A method for producing methyl-1,2-benzoxathiin-8-ylsulfonamide has been discovered.

Within the scope of the present invention, Hal represents a chlorine atom, a bromine atom or an iodine atom, preferably a chlorine atom and a bromine atom.

formula! The reaction product represented by is reacted directly or as a corresponding inocyanate or carbamate by a known method to produce a sulfonylurea herbicide.

The starting compound of formula II is known and is 2,3-dihydro-
2-Methylbenzo(b) can be produced by halogenating furan.

Commercially available chlorosulfonic acid is conveniently used to carry out the first step (■→■) of the process according to the invention. At least 3 mol of chlorosulfonic acid are used per mol of compound of formula II. A substantial excess of chlorosulfonic acid, for example at least 5 moles relative to the compound of formula II, is used for f.
f7) is advantageous. In individual embodiments of the process, cross-sulfonic acid can be used simultaneously as reactant and as solvent. However, usually the reaction (II→
Ill) is carried out in an inert solvent. Suitable solvents are carbon disulfide, ethyl acetate, and tetrahydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, 1,2-dichloroethane and 1,2-dichloroethylene, tetrachloroethylene, chloroform/or dichlorobenzene. The preferred solvent is methylene chloride, 1
．． 2-dichloroethane and chloroform.

The reaction temperature is usually -10 to +80°C, preferably -
It is within the range of 10 to +60°C.

In a preferred embodiment of the first reaction step (■→■), the compound of formula (■) in which Hal represents a chlorine atom or a bromine atom is prepared by adding the desired compound of formula II in an inert solvent at a temperature of -10 to +80°C. chlorosulfonic acid in an amount of at least 3 moles of chlorosulfonic acid per mole of the compound of formula II. In a most preferred embodiment of the process of the invention, the reaction (II-)I) is carried out at -10 to +60
This is carried out by reacting with at least 5 mol of chlorosulfonic acid per mol of compound of formula II in methylene chloride, 1,2-dichloroethane or chloroform in the temperature range of .degree.

The conversion of the sulfonyl chloride of formula III into the corresponding sulfo/amide of formula IV can be carried out under the conditions customarily used for reaction steps which are known per se, e.g.
This is carried out by treating a compound of formula I with aqueous ammonia under normal pressure and room temperature, or by treating a compound of formula III with ammonia in an inert solvent, optionally in the presence of an acid acceptor. Examples of suitable solvents and acid acceptors are listed below: carbonates such as sodium carbonate and potassium carbonate, bicarbonates such as sodium bicarbonate and potassium bicarbonate, oxides such as calcium oxide and magnesium oxide.

Hydroxides such as sodium hydroxide, potassium hydroxide, calcium hydroxide or magnesium hydroxide; ethers such as diethyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether or diethylene glycol dimethyl ether; or such as cyclohexane, benzene, toluene or xylene. hydrocarbons. Reaction with ammonia aqueous solution is preferred.

Dehalogenation by catalytic reduction of a compound of formula IV to obtain a compound of formula ■ usually involves reaction with hydrogen in the presence of an acid acceptor in an inert solvent under mild conditions at room temperature and atmospheric pressure. It is done well. The catalysts used are noble metal catalysts such as platinum or palladium, usually in the form of platinum oxide, platinum black catalyst, platinum on barium sulfate, palladium black catalyst or palladium on carbon.

The most widely used catalyst is palladium on carbon as a commercially available 5% palladium/carbon catalyst.

Commonly used acid acceptors include carbonates such as sodium carbonate, potassium carbonate or calcium carbonate, bicarbonates such as sodium bicarbonate or potassium bicarbonate, oxides such as magnesium oxide or calcium oxide. , and preferably trimethylamine, triethylamine, diazabicyclo[2,2,23octane, 1,8-diazabicyclo[5,4,·0]-undec-7-ene, 1,5-diazabicyclo[4,·3
．． -0] Tertiary amines such as none-5-dine, pyridine, quinoline or isoquinol.

Suitable solvents include ethers such as diethyl ether, tetrahydrofuran or dioxane; esters such as ethyl acetate, methanol, ethanol,
n-propa/-lumoL< is an alcohol such as 1-propatool; and a hydrocarbon such as hentane, hexane, cyclohexa/, benzene, toluene or quinolene. In a preferred embodiment of the process, the compound of formula IV is prepared in tetrahydrofuran at normal pressure from 20 to 2
It is produced by reaction with hydrogen in the presence of 5% palladium on carbon catalyst at a temperature of 5°C.

The catalytic reduction of the non-aromatic double bonds of the compound of formula ■ in the final reaction step (■→I) is carried out under more aggressive conditions than in the previous reaction step (■→V), i.e. the pressure and temperature of the hydrogen atmosphere. This is done by advantageously increasing both. Preferred conditions are a pressure of 1 to 10 pars and a temperature range of 30 to 60°C. The catalyst and solvent are selected from the same group as indicated in the previous reaction step. In a preferred embodiment of the process, the compound of formula (1) is hydrogenated in tetrahydrofuran at a temperature of 30 to 60° C. under a pressure of 1 to 5 pars in the presence of a palladium on 5'4 carbon catalyst.

A preferred embodiment of the process of the invention for the preparation of compounds of formula I is a compound of formula II in which Ha/ represents a bromine or chlorine atom.
is reacted with at least 5 moles of chlorosulfonic acid per mole of compound of formula II in methylene chloride, 1,2-dichloroethane or chloroform in the temperature range from -10 to +60'C, resulting in a compound of formula II. Treatment of the sulfonyl chloride with aqueous ammonia solution and catalytic reduction of the resulting sulfonamide of formula IV with hydrogen in the presence of a palladium on carbon catalyst in tetrahydrofuran at normal pressure in the temperature range from 20 to 25°C. and reducing the resulting dehalogenated sulfonamide of formula (1) in the presence of a 5% palladium on carbon catalyst in the temperature range of 50 to 50° C. under a pressure of t-1 to 5 bar. Consisting of

(Example) The present invention will be explained in more detail with reference to the following examples. Example P5Fi is to be understood as representing a second reaction step variant of Example P1.

Preparation Examples Example P1: 5,4-dihydro-2,2-dioxo-3
-Methyl-1,2-benzoxathiin-8-ylsulfo/amide a) S-bromo-2,3-dihydro-2-methylbenzo[bl Bromine 215d in furamethylene chloride 450d (D solution 2,3-dihydro-2 -Methylbenzo (bl furan 5
62.5II, methylene chloride 16001117,
Water 1600R1 and sodium bicarbonate! 152.55
1 over a period of 21/2 hours. After stirring the mixture at the same temperature for an additional 11/2 hours, the aqueous layer was completely separated and extracted twice with 300 d of methylene chloride. The combined organic layers are washed twice with 250 g of water, dried over sodium sulfate, and then concentrated. After removing all constituents having a boiling point below 99°C under Lipard pressure, 7 g of 5-bromo-2,3-dihydro-2-methylbenzo (bl furan 75α) is obtained as a residue.

b) 6-bromo-2,2-dioxo-3-methy-
1,3-benzoxathiin-8-ylsulfonyl chloride 400 d of chlorosulfonic acid was dissolved in 5-bromo 2°5-dihydro-2-methylbenzo (bl) 160 g of furan was dissolved in anhydrous chloroform A 46 G ml K We L, -7°C
was added dropwise over 20 minutes to the solution cooled to 15°C.
Stir for 15 minutes at a temperature of
A mixture of 100O and 500 ml of chloroform was
Add dropwise over a period of minutes while stirring. After the mixture is kept stirring at 0° C. for 15 minutes, the organic layer is separated and the aqueous layer is extracted three times with 250 portions of chloroform. The combined ams were washed with 150 d of water, dried over sodium formate, and concentrated to give 6-6 as an oily residue that could be further reacted directly.
Bromo 2,2-dioquino-3-methyl-1,2-benzoxathiin-8-ylsulfonyl chloride 180g
t-get.

C) 6-bromo2,2-dioquine-3-methy-
1,2-benzoxathiin-8-ylsulfonamide 6-promo 2,2-dioxo-3-methyl-1,2-
Benzoxathiin-8-ylsulfonyl chloride 18
A solution prepared by dissolving 0 g of tetrahydrofuran 500*/Ic was added dropwise to 30 g of aqueous ammonia solution 307d over 30 minutes. The mixture was stirred at 20°C for 50 minutes and then concentrated under reduced pressure at 45°C to give 6-bro7-2,2-dioquino-3-methyl-1,2-benzoxathiin-8-ylsulfone with a melting point of 243-245°C. Amide 6521 (crystallized from ethanol) is obtained.

d) 2,2-dioquino-6-methyl-1,2-benzoxathiin-8-ylsulfonamide 6-bro7-2,2
-Dioquino-5-methyl-1,2-benzoxathiine-
8-ylsulfonamide 120II was dissolved in 2.4% tetrahydrofuran and the solution was dissolved in 41% triethylamide.
40 g of hydrogen at normal pressure and a temperature range of 20 to 25° C. in the presence of 5 g and 12.0 g of 5-blue palladium catalyst on carbon.
Reduce minutes. The mixture is filtered, the p-liquid is concentrated and the residue is treated with 1300 ml of hot 90% aqueous ethanol.

Separate the insoluble components and cool the solution to 0°C. Separating and drying the precipitate yields 70 g of 2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide having a melting point of 204-205°C.

e) 2.2-Dioquine-4-methyl-1,2-benzogisathiin-8-ylsulfonamide 1α011tf dissolved in 200 d of trahydrofuran and the solution mixed with 2.0 g of a catalyst of 5% palladium on carbon. Reduction with hydrogen in the presence of hydrogen at a pressure of 4 bar and a temperature of 40° C. for 2172 hours. After removing the catalyst.

Concentrate the solution, and the residue tl - 70% aqueous ethanol solution 1
When crystallized from 20 ml, it has a melting point of 185-186°C.
．． 4-dihydro-2,2-dioquine-3-methyl-1,
2-penzoxatii/-8-ylsulfonamide 9.0
g gets rel.

Example P2: N-(3,4-dihydro-2,2-dioquino-3-methyl-1,2-benzoxathiin-8-ylsulfonyl)-N'-(4-methquine-6-methylpyrimidine-2- 3.4-dihydro-2,2-dioquino-5-methyl-1
,2-benzoxathiin-8-ylsulfonamide 15
3fl, 1,8-diazabicyclo[5.4.0]undec-7-nin 1.84go, N-(4-methoxy-6-methylpyrimidin-2-yl)phenylcarbamate h2
y and 'cF anhydrous dioxane 55 df Stir for 45 minutes at a temperature in the range of 20-25°C. Concentrate the mixture and leave an oily residue? Triturate with 1t't ether and 1N hydrochloric acid 14111. The resulting crystalline precipitate was completely separated, washed with water, and dried to give N-(3°4-dihydro-2,2-dioquino-5-methyl-1,2-benzoxathiin-8-yl) with a melting point of 215-218°C. sulfonyl) -N'-(4-methoxy-6-methylpyrimidin-2-yl) urine g a, 9
b I is obtained.

Example P6: Preparation of 6-pro;2,2-dioquino-3-methyl-1,2-be/zoxathiin-8-ylsulfonyl chloride Chlorosulfone [d133m'l(,5-7'0-E-
-2,s-dihydro-2-methylbenzo(b)furan 4
2.617 was dissolved in chloroform at 120 mA JC at a temperature of 40 to 50°C over 30 minutes. The mixture is heated under reflux for 4 hours, cooled to 0° C. and then added dropwise over 30 minutes to a mixture of 400 g of ice, 500 m of water and 100 at of dichloroform. The organic layer is separated and the aqueous layer is extracted five times with each 100-ml portion of chloroform. The combined organic layers were washed with water and concentrated to give 6-promo 2゜2.
-Dioquino-3-methyl-1,2-benzoxathiine-
8-ylsulfonyl chloride 72. '2V is obtained as an oily residue.

Claims (11)

[Claims] (1) The following formula II: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) 5-halo-2,3-dihydro- represented by (in the formula, Hal represents a chlorine atom, a bromine atom, or an iodine atom)
2-Methylbenzo[b]furan is reacted with chlorosulfonic acid to form the following formula III: ▲Mathematical formulas, chemical formulas, tables, etc.▼(III) (In the formula, Hal represents a chlorine atom, bromine atom, or iodine atom). 6-halo-2,2-dioxo-
3-Methyl-1,2-benzoxathiin-8-ylsulfonyl chloride is produced, and this sulfonyl chloride is converted to the following formula IV using ammonia: or iodine atom) to 6-halo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-yl sulfonamide in the presence of a tertiary amine and a noble metal catalyst. 2,2-dioxo-3-methyl-1,2- expressed by dehalogenation with hydrogen and the following formula V: ▲Mathematical formula, chemical formula, table, etc.▼(V)
The following formula I, which is characterized by hydrogenation of benzoxathiin-8-ylsulfonamide in the presence of a noble metal catalyst: ▲Mathematical formulas, chemical formulas, tables, etc.▼3,4-dihydro-2, represented by (I) 2-dioxo-5
-Method for producing methyl-1,2-benzoxathiin-8-ylsulfonamide. (2) The method according to claim 1, wherein in the above formula, Hal represents a chlorine atom or a bromine atom. (3) The method according to claim 1, characterized in that the reactions in all stages are carried out at -10 to +80°C, preferably -10 to +60°C. (4) The method according to claim 1, characterized in that each reaction step is carried out in an inert solvent. (5) The reaction to obtain a compound of formula III from a compound of formula II is carried out in methylene chloride, 1,2-dichloroethane or chloroform, the reaction to obtain a compound of formula IV from a compound of formula III is carried out in water, and the reaction to obtain a compound of formula IV from a compound of formula III is carried out in water; 5. A process according to claim 4, characterized in that the reaction for obtaining a compound of formula V from a compound of formula V and the reaction for obtaining a compound of formula I from a compound of formula V are carried out in tetrahydrofuran. (6) Reaction to obtain a compound of formula III from a compound of formula II using at least 3 moles of chlorosulfonic acid per mole of compound of formula II in an inert solvent between -10 and +
The method according to claim 1, characterized in that it is carried out in a temperature range of 80°C. (7) A reaction to obtain a compound of formula III from a compound of formula II,
Claims characterized in that the process is carried out in methylene chloride, 1,2-dichloroethane or chloroform with at least 5 mol of chlorosulfonic acid per mole of compound of formula II in the temperature range from -10 to +60°C. The method described in Section 6. (8) The method according to claim 1, characterized in that the reaction of the compound of formula III to the compound of formula IV is carried out in an aqueous ammonia solution. (9) Dehalogenation of the compound of formula IV to obtain the compound of formula V in tetrahydrofuran under normal pressure between 20 and 2
Process according to claim 1, characterized in that it is carried out with hydrogen at 5° C. and in the presence of 5% palladium on carbon catalyst. (10) Hydrogenation of a compound of formula V to obtain a compound of formula I in tetrahydrofuran at a temperature range of 30 to 50° C. under a pressure of 1 to 5 bar and over 5% palladium on carbon catalyst. 2. A method according to claim 1, characterized in that the method is carried out in the presence of (11) A compound of formula II in which Hal represents a bromine atom or a chlorine atom at a temperature range of -10 to +60°C,
at least 5 per mole of compound of formula II in methylene chloride, 1,2-dichloroethane or chloroform.
mol of chlorosulfonic acid, the resulting sulfonyl chloride of formula III is treated with aqueous ammonia, and the resulting sulfonamide of formula IV is reacted with a sulfonamide of formula IV in tetrahydrofuran.
5% on carbon at normal pressure and temperature range of 20 to 25°C
dehalogenated by catalytic reduction with hydrogen in the presence of a palladium catalyst of Process according to claim 1, characterized in that the reduction is carried out in the presence of 5% palladium catalyst.